Simultaneous determination of 3-n-butylphthalide and its metabolite 10-hydroxy-butylphthalide in rat plasma using liquid chromatography-tandem mass spectrometry and application to a pharmacokinetic study.
Biomed Chromatogr
; 35(11): e5184, 2021 Nov.
Article
in En
| MEDLINE
| ID: mdl-34060121
ABSTRACT
3-n-Butylphthalide (NBP) is a potent drug for the treatment of ischemic stroke. The aim of this study was to develop a simple and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for the simultaneous determination of NBP and its circulating metabolite 10-hydroxy-NBP in rat plasma using senkyunolide I as the internal standard (IS). The analytes and IS were extracted from the plasma by ethyl acetate-ethyl ether (15, v/v) and then separated on an ACQUITY BEH C18 column (2.1 × 50 mm, 1.7 µm). The mobile phase consisted of water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid, which was delivered at a flow rate of 0.3 mL/min with gradient elution. MS detection was achieved under selective reaction monitoring mode with precursor-to-product transitions at m/z 191.1 > 145.1 for NBP, m/z 207.1 > 171.1 for 10-hydroxy-NBP and m/z 207.1 > 161.1 for IS, respectively. The assay showed excellent linearity over the concentration range of 0.5-1000 ng/mL for both analytes, with correlation coefficient greater than 0.998. The other validation parameters were all within the required limits. The validated UPLC-MS/MS method has been further applied to the pharmacokinetic study of NBP and 10-hydroxy-NBP in rats after they were orally administered with NBP (30 mg/kg).
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Benzofurans
/
Chromatography, High Pressure Liquid
/
Tandem Mass Spectrometry
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biomed Chromatogr
Year:
2021
Type:
Article
Affiliation country:
China